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European	Journal	of	Chemistry	2	(3)	(2011)	317‐323	

	
European	Journal	of	Chemistry	

ISSN	2153‐2249	(Print)	/	ISSN	2153‐2257	(Online)		2011	EURJCHEM	
DOI:10.5155/eurjchem.2.3.317‐323.420	

	
	

	

	

European	Journal	of	Chemistry	
Journal	homepage:	www.eurjchem.com	

	 	 	

Reactions	with	hydrazonoyl	halides	65:	Synthesis	of	some	new		
1,3,4‐thiadiazoles	and	triazolino[4,3‐a]pyrimidines	containing	pyrazole	moiety	

Abdou	Osman	Abdelhamid*,	Abdelgawad	Ali	Fahmi	and	Karema	Noury	Mahmoud	Halim	

Department	of	Chemistry,	Faculty	of	Science,	Cairo	University,	Giza,	12613,	Egypt	

*Corresponding	author	at:	Department	of	Chemistry,	Faculty	of	Science,	Cairo	University,	Giza,	12613,	Egypt.	Tel.:	+202.35676573;	fax:	+202.35727556.		
E‐mail	address:	abdelhamid45@gmail.com	(A.	O.	Abdelhamid).	

	
	

	 	

	 	 	
ARTICLE	INFORMATION	 	 ABSTRACT
Received:	19	March	2011	
Received	in	revised	form:	24	April	2011	
Accepted:	02	May	2011	
Online:	30	September	2011	

KEYWORDS	

	 2,3‐Dihydro‐1,3,4‐thiadiazoles,	and	triazolino[4,3‐a]pyrimidines	containing	pyrazole	moieties
were	 prepared	 from	 the	 reaction	 of	 alkyl	 2‐[1‐(4‐cyano‐1,5‐diphenyl‐1H‐pyrazol‐3‐
yl)ethylidene]hydrazinecarbodithioate	and	pyrimidine‐2‐thione	derivatives	with	appropriate
hydrazonoyl	halides.	The	structures	of	all	the	newly	synthesized	compounds	were	confirmed
by	elemental	analyses,	spectral	data,	and	alternative	route	of	synthesis	whenever	possible.		

Pyrazoles		
Nitrilimines	
1,3,4‐Thiadiazoles	
Hydrazonoyl	halides	
Pyrimidine‐2‐thione	
Triazolino[4,3‐a]pyrimidines	

	
1.	Introduction	
	

1,3,4‐Thiadiazoles	 have	 been	 screened	 for	 their	
antibacterial	 and	 antifungal	 activities	 [1‐4],	 anti‐inflammatory	
[5],	 anti‐tuberculosis	 [6]	 and	 anticancer	 [7]	 activity.	 Also,	
pyrazoles	 and	 annelated	 pyrazoles	 have	 long	 been	 known	 to	
exhibit	 diverse	 biological	 activities	 [8,	 9,	 10‐13].	 These	
activities	 include	 their	 use	 as	 cAMP	 phosphodiesterase	
inhibitors,	 antipyretic,	 antitumor,	 hypnotic	 and	 herbicidal	
agents.		It	was	of	value	to	combine	the	two	moieties	in	a	series	
of	derivatives	with	the	objective	of	investigating	their	expected	
biological	activities.	As	an	extension	of	our	study	[14‐20]	and	as	
a	 part	 of	 our	 program	 aiming	 at	 the	 synthesis	 of	 different	
heterocyclic	 derivatives,	 we	 report	 here	 the	 convenient	
synthesis	 of	 2,3‐dihydro‐1,3,4‐thiadiazoles	 and	 triazolino[4,3‐
a]pyrimidines	containing	pyrazole	moiety.	
	
2.	Experimental	
	
2.1.	Instrumentation	
	

All	melting	 points	were	 determined	 on	 an	 Electrothermal	
melting	point	apparatus	and	are	uncorrected.	 IR	 spectra	were	
recorded	 (KBr	 discs)	 on	 a	 Shimadzu	 FT‐IR	 8201	 PC	
spectrophotometer.	 1H	and	 13C	NMR	spectra	were	 recorded	 in	
CDCl3	and	(CD3)2SO	solutions	on	a	Varian	Gemini	200	MHz	and	
300	MHz	spectrometer	and	chemical	shifts	are	expressed	 in	δ	
units	 using	 TMS	 as	 internal	 reference.	 Mass	 spectra	 were	
recorded	on	a	Shimadzu	GCMS‐QP1000	EX	mass	spectrometer,	
operating	 at	 70	 eV.	 Elemental	 analyses	 were	 carried	 out	 at	
Microanalytical	Center	of	Cairo	University,	Giza	12613,	Egypt.	
	

2.2.	Synthesis	of	alkyl	2‐[1‐(4‐cyano‐5‐diphenyl‐1‐
substituted‐1H‐pyrazol‐3‐yl)ethylidene]hydrazine‐
carbodithioate	(3a	and	3b)	
	

A	mixture	 of	 the	 appropriate	 of	1a	 or	1b	 [23]	 (10	mmol)	
and	 the	 appropriate	 alkyl	 hydrazinecarbodithioates	 2a	 or	 b	
[24]	(10	mmol)	in	2‐propanol	(10	mL)	was	boiled	under	reflux	
for	30	minutes.	The	resulting	solid	so	formed	after	cooling	was	
collected	and	crystallized	 from	ethanol	 to	give	yellow	crystals	
3a‐d	(Scheme	1)	

Methyl	 2‐[1‐(4‐cyano‐1,5‐diphenyl‐1H‐pyrazol‐3‐yl)	 ethyl‐
idene]hydrazinecarbo‐dithioate	 (3a):	 Yellow	 solid.	 Yield:	 76%.	
M.p.:	 180‐182	 oC.	 IR	 (KBr,	 cm‐1):	 3039	 (CH,	 aromatic),	 2922	
(CH,	 aliphatic),	 2225	 (CN),	 1596	 (C=C),	 1364	 (CH3)	 cm‐1.	 1H	
NMR	(300	MHz,	(CD3)2SO,	,	ppm):	2.09	(s,	3H,	CH3),	2.40	(s,	3H,	
CH3),	 7.45‐7.49	 (m,	 10	 H,	 ArH's),	 7.96	 (s,	 br.,	 1H,	 NH).	 Anal.	
Calcd.	 for	 C20H17N5S2	 (391.51):	 C,	 61.36;	 H,	 4.38;	 N,	 17.89;	 S,	
16.38.	Found:	C,	61.58;	H,	4.12;	N,	18.01;	S,	16.15%.	

Benzyl	 2‐[1‐(4‐cyano‐1,5‐diphenyl‐1H‐pyrazol‐3‐yl)ethyl‐
idene]hydrazinecarbo‐dithioate	 (3b):	 Yellow	 solid.	 Yield:	 81%.	
M.p.:	 192‐194	 oC.	 IR	 (KBr,	 cm‐1):	 3038	 (CH,	 aromatic),	 2921	
(CH,	aliphatic),	2224	(CN),	1609	(C=C),	1433	(CH2),	1364	(CH3)	
cm‐1.	 1H	NMR	 (200	MHz,	 (CH3)2SO,	,	 ppm):	2.33	 (s,	 3H,	 CH3),	
4.37	 (s,	 2H,	 CH2),	 7.27‐7.49	 (m,	 15	H,	 ArH's),	 7.96	 (s,	 br.,	 1H,	
NH).	Anal.	Calcd.	 for	C26H21N5S2	 (467.61):	C,	66.78;	H,	4.53;	N,	
14.98;	S,	13.71.	Found:	C,	66.89;	H,	4.62;	N,	14.75;	S,	13.55%.	

Methyl	 2‐{1‐[4‐cyano‐1‐(4‐methylphenyl)‐5‐phenyl‐1H‐pyra‐
zol‐3‐yl]ethylidene}‐hydrazinecarbodithioate	 (3c):	 Yellow	 solid.	
Yield:	 85%.	 M.p.:	 198‐200	 oC.	 IR	 (KBr,	 cm‐1):	 3044	 (CH,	
aromatic),	 2922	 (CH,	 aliphatic),	 2227	 (CN),	 1612	 (C=C),	 1375	
(CH3)	cm‐1.	 1H	NMR	(200	MHz,	 (CH3)2SO,	,	ppm):	2.33	(s,	3H,	
CH3),	 2.55	 (s,	 3H,	 CH3),	 2.60	 (s,	 3H,	 CH3),	 7.27‐7.47	 (m,	 9	 H,	
ArH's),	7.48	(s,	br.,	1H,	NH).		



318	 Abdelhamid	et	al.	/	European	Journal	of	Chemistry	2	(3)	(2011)	317‐323	
	

 

	
	

Scheme	1
	
	
Anal.	Calcd.	for	C21H19N5S2,	(405.54):	C,	62.19;	H,	4.72;	N,	17.27;	
S,	15.81.	Found:	C,	62.00;	H,	4.94;	N,	17.35;	S,	15.62%.	

Benzyl	 2‐{1‐[4‐cyano‐1‐(4‐methylphenyl)‐5‐phenyl‐1H‐pyra‐
zol‐3‐yl]ethylidene}‐hydrazinecarbodithioate	(3d):	Yellow	solid.	
Yield:	 88%.	 M.p.:	 208‐210	 oC.	 IR	 (KBr,	 cm‐1):	 3052	 (CH,	
aromatic),	 2924	 (CH,	 aliphatic),	 2224	 (CN),	 1612	 (C=C),	 1438	
(CH2),	1375	(CH3)	cm‐1.	 1H	NMR	(200	MHz,	(CH3)2SO,	,	ppm):	
2.30	(s,	3H,	CH3),	2.62	(s,	3H,	CH3),	4.54	(s,	2H,	CH2),	7.27‐7.46	
(m,	 14	 H,	 ArH's),	 7.47	 (s,	 br.,	 1H,	 NH).	 Anal.	 Calcd.	 for	
C27H23N5S2	(481.64):	C,	67.33;	H,	4.81;	N,	14.54;	S,	13.32.	Found:	
C,	67.42;	H,	5.01;	N,	14.38;	S,	13.51%.	
	
2.3.	Synthesis	of	5‐{[1‐(4‐cyano‐1,5‐diphenyl‐1H‐pyrazol‐3‐
yl)‐ethylidene]‐hydrazono}‐4‐phenyl‐2‐substituted	4,5‐
dihydro‐[1,3,4]thiadiazole	(8a‐e)	and	5‐{[1‐(4‐Cyano‐5‐
phenyl‐1‐p‐tolyl‐1H‐pyrazol‐3‐yl)‐ethylidene]‐hydrazono}‐4‐
phenyl‐2‐substituted	4,5‐dihydro‐[1,3,4]thiadiazole	(10a‐e)	
	

A	mixture	 of	 the	 alkyl	 carbodithioate	3a,	3b	or	3c,	3d	 (5	
mmol),	 the	appropriate	hydrazonoyl	halides	4a‐e	(5	mmoles),	
and	triethylamine	(0.75	mL,	0.005	mol)	in	ethanol	(20	mL)	was	
stirred	 for	 2	 h	 at	 room	 temperature.	 The	 resulting	 solid	 was	
collected	 and	 recrystallized	 to	 give	 2,3‐dihydro‐1,3,4‐
thiadiazoles	8a‐e	and	10a‐e,	respectively	(Scheme	1).	

Alternative	 Method:	 A	 mixture	 of	 ethyl	 2‐hydrazino‐3‐
phenyl‐1,3,4‐thiadiazoline‐5‐carboxylate	 [25]	 (9a)	 (1.32	 g,	 5	
mmol)	and	the	appropriate	3‐acetylpyrazole	1a	or	1b	(5	mmol)	
in	2‐propanol	(10	mL)	was	stirred	for	2	h	at	room	temperature.	
The	 resulting	 solids	 were	 collected	 and	 recrystallized	 from	
ethanol	to	give	product	identical	with	8a	and	10a,	which	were	
obtained	by	the	above	method).	

Ethyl	 5‐{[1‐(4‐cyano‐1,5‐diphenyl‐1H‐pyrazol‐3‐yl)‐ethyl‐
idene]‐hydrazono}‐4‐phenyl‐4,5‐dihydro‐[1,3,4]thiadiazole‐2‐
carboxylate	(8a):	Yellow	solid.	Yield:	76	%.	M.p.:	329‐331	oC.	IR	
(KBr,	 cm‐1):	 3059	 (CH,	 aromatic),	 2922	 (CH,	 aliphatic),	 2225	
(CN),	 1734	 (CO,	 ester),	 1671	 (CO),	 1596	 (C=C),	 1433	 (CH2),	
1364	(CH3)	cm‐1.		1H	NMR	(200	MHz,	(CH3)2SO,	,	ppm):	1.25	(t,	
3H,	 J	 =	7	Hz,	CH2CH3),	 2.49	 (s,	3H,	CH3),	 4.37	 (q,	2H,	 J	 =	7	Hz,	
CH2CH3),	 7.45‐7.95	 (m,	 15	 H,	 ArH's).	 13C	 NMR	 (200	 MHz,	
(CH3)2SO,	,	 ppm):	 13.34,	 15.41,	 62.72,	 99.21,	 120.25,	 125.56,	
126.12,	127.23,	129.23,	129.67,	130.42,	130.83,	140.58,	143.56,	
144.24,	 147.31,	 151.11,	 160.56,	 161.62,	 177.83.	MS	 (m/e,	%):	
534	 (M+1,	 100%),	 519	 (5.4%),	 501	 (3.7%),	434	 (27.5%),	 401	
(4.21%),	 372	 (6.7%),	 272	 (8%),	 243	 (22%),	 189	 (11%),	 179	
(15%),	140	(14%),	134	(13%),	1o2	(10%),	90	(34%),	77	(43%),	
64	 (10%).	 Anal.	 Calcd.	 for	 C29H23N7O2S	 (533.16):	 C,	 65.28;	 H,	
4.34;	 N,	 18.37;	 S,	 6.01.	 Found:	 C,	 65.41;	 H,	 4.28;	 N,	 18.29;	 S,	
6.21%.	



Abdelhamid	et	al.	/	European	Journal	of	Chemistry	2	(3)	(2011)	317‐323	 319	
 

 
 

3‐{1‐[(5‐Acetyl‐3‐phenyl‐3H‐[1,3,4]thiadiazol‐2‐ylidene)‐
hydrazono]‐ethyl}‐1,5‐diphenyl‐1H‐pyrazole‐4‐carbonitrile	 (8b):	
Pale	yellow	solid.	Yield:	75%.	M.p.:	298‐300	oC.	IR	(KBr,	cm‐1):	
3054	 (CH,	 aromatic),	 2924	 (CH,	 aliphatic),	 2230	 (CN),	 1665	
(CO),	 1596	 (C=C),	 1428	 (CH3)	 cm‐1.	 	 1H	 NMR	 (200	 MHz,	
(CH3)2SO,	,	ppm):	2.08	(s,	3H,	CH3),	2.49	(s,	3H,	CH3),	7.42‐7.98	
(m,	15	H,	ArH's).	MS	(m/e,	%):	502	(M‐1,	9.7%),	437	(9.87%),	
363	 (10.36.7%),	 301	 (10.17%),	 286	 (18%),	 284	 (13.56),	 272	
(21%),	271	(23%),	270	(30%),	259	(14.8%),	244	(20.6%),	233	
(11%),	 232	 (11%),	 210	 (11.7%),	 191	 (20%),	 180	 (22%),	 169	
(13.3),	 163	 (11.5%),	 151	 (19.5%),	 149	 (24.8%),	 140	 (20%),	
136	 (17.2%),	 126	 (27.0%),	 111	 (32.8%),	 109	 (36%),	 90	
(100%),	 77	 (97.3%),	 65	 (36.1%).	 Anal.	 Calcd.	 for	 C28H21N7OS			
(503.58):	C,	66.78;	H,	4.20;	N,	19.47;	S,	6.37.	Found:	C,	66.92;	H,	
4.00;	N,	19.13;	S,	6.52%.	

3‐{1‐[(5‐Benzoyl‐3‐phenyl‐3H‐[1,3,4]thiadiazol‐2‐ylidene)‐
hydrazono]‐ethyl}‐1,5‐diphenyl‐1H‐pyrazole‐4‐carbonitrile	 (8c):	
Brown	solid.	Yield:	73%.	M.p.:	311‐13oC	(DMF).	IR	(KBr,	cm‐1):	
3059	 (CH,	 aromatic),	 2925	 (CH,	 aliphatic),	 2225	 (CN),	 1660	
(CO),	 1596	 (C=C),	 1395	 (CH3)	 cm‐1.	 	 1H	 NMR	 (200	 MHz,	
(CH3)2SO,	,	ppm):	2.49	(s,	3H,	CH3),	7.42‐7.98	(m,	20	H,	ArH's).	
MS	 (m/e,	 %):	 566	 (M+1,	 1.1%),	 407	 (1%),	 357	 (67%),	 340	
(20.5%),	149	(7.3%),	135	(13.8),	105	(84.3%),	271	(23%),	98	
(36.7,	912	(34.8%),	77	(100%),	68	(39.6%),	65	(22.56%).	Anal.	
Calcd.	 for	 C33H23N7OS,	 (565.17):	 C,	 70.07;	H,	 4.10;	N,	 17.33;	 S,	
5.67.	Found:	C,	69.81;	H,	3.82;	N,	17.25;	S,	5.82%.	

5‐{[1‐(4‐Cyano‐1,5‐diphenyl‐1H‐pyrazol‐3‐yl)‐ethylidene]‐
hydrazono}‐4‐phenyl‐2‐phenylcarbamoyl‐4,5‐dihydro‐[1,3,4]	
thiadiazole	 (8d):	Pale	 yellow	 solid.	 Yield:	 78%.	M.p.:	 322‐324	
oC.	IR	(KBr,	cm‐1):	3380	(NH),	3060	(CH),	2923	(CH,	aliphatic),	
2225	 (CN),	1663	 (CO),	1596	 (C=C),	1346	 (CH3)	 cm‐1.	 	 1H	NMR	
(200	MHz,	(CH3)2SO,	,	ppm):	2.72	(s,	3H,	CH3),	7.42‐7.98	(m,	20	
H,	 ArH's),	 9.82	 (s,	 br.,	 1H,	 NH).	 Anal.	 Calcd.	 for	 C33H24N8OS	
(580.66):	C,	68.26;	H,	4.17;	N,	19.30;	S,	5.52.	Found:	C,	68.43;	H,	
4.31;	N,	19.12;	S,	5.34%.	

3‐({2‐[1,2‐diaza‐3‐(4‐cyano‐1,5‐diphenyl(2‐pyrazolin‐3‐
yl)but‐2‐enylidene]‐3‐phenyl(1,3,4‐thiadiazolin‐5‐yl)}carbonyl)‐
1‐(4‐methylphenyl)‐5‐phenylpyrazole‐4‐carbonitrile	 (8e):	 Deep	
red	 solid.	 Yield:	 78	%.	M.p.:	 243‐245	 oC.	 IR	 (KBr,	 cm‐1):	 3032	
(CH,	 aromatic),	 2926	 (CH,	 aliphatic),	 2228	 (CN),	 1665	 (CO),	
1600	(C=C),	1378	(CH3)	cm‐1.	 	 1H	NMR	(200	MHz,	(CH3)2SO,	,	
ppm):	2.33	 (s,	3H,	CH3),	2.64	 (s,	3H,	CH3),	 7.07‐7.95	 (m,	24	H,	
ArH's).	 MS	 (m/e,	 %):	 747	 (M+1,	 0.12%),	 716	 (0.45%),	 688	
(0.14%),	 556	 (6%),	 542	 (0.8%),	 483	 (0.2%),	 286	 (10%),	 270	
(34%),	 258	 (6.5%),	 243	 (20.8%),	 216	 (10.9%),	 180	 (16.2%),	
155	(7.4%),	127	(11%),	114	(6%),	103	(24.6%),	91	(46%),	(77	
(100%),	 65	 (29.6%).	 Anal.	 Calcd.	 for	 C44H30N10OS	 (746.84):	 C,	
70.76;	 H,	 4.05;	 N,	 18.75;	 S,	 4.29.	 Found:	 C,	 70.46;	 H,	 3.82;	 N,	
18.58;	S,	4.12%.	

Ethyl	 5‐{[1‐(4‐cyano‐5‐phenyl‐1‐p‐tolyl‐1H‐pyrazol‐3‐yl)‐
ethylidene]‐hydrazono}‐4‐phenyl‐4,5‐dihydro‐[1,3,4]thiadiazole‐
2‐carboxylate	(10a):	Yellow	solid.	Yield:	77%.	M.p.:	322‐324	oC.	
IR	(KBr,	cm‐1):	3044	(CH,	aromatic),	2922	(CH,	aliphatic),	2225	
(CN),	 1670	 (CO),	 1611	 (C=N),	 1545	 (C=C),	 1439	 (CH2),	 1375	
(CH3)	cm‐1.		1H	NMR	(200	MHz,	(CH3)2SO,	,	ppm):	1.33	(t,	3H,	J	
=	7	Hz,	CH2CH3),	2.73	(s,	3H,	CH3),	2.89	(s,	3H,	CH3),	4.41	(q,	2H,	
J	=	7	Hz,	CH2CH3),	7.42‐7.98	(m,	14	H,	ArH's).	MS	(m/e,	%):	548	
(M+1,	 17.8%),	 547	 (M+,	 34.4%),	 496	 (13.3.7%),	 284	 (35.6%),	
135	(35.3%),	91	(100%),	77	(78%),	65	(46.7%).	Anal.	Calcd.	for	
C30H25N7O2S,	547.63,	C,	65.80;	H,	4.60;	N,	17.90;	S,	5.86.	Found:	
C,	66.02;	H,	4.72;	N,	17.82;	S,	6.00%.	

3‐{1‐[(5‐Acetyl‐3‐phenyl‐3H‐[1,3,4]thiadiazol‐2‐ylidene)‐
hydrazono]‐ethyl}‐5‐phenyl‐1‐p‐tolyl‐1H‐pyrazole‐4‐carbonitrile	
(10b):	Yellow	solid.	Yield:	76%.	M.p.:	312‐314	oC.	 IR	(KBr,	cm‐

1):	3044	(CH,	aromatic),	2922	(CH,	aliphatic),	2227	(CN),	1676	
(CO),	 1609	 (C=N),	 1375	 (CH3)	 cm‐1.	 	 1H	 NMR	 (200	 MHz,	
(CH3)2SO,	,	ppm):	2.33	(s,	3H,	CH3),	2.73	(s,	3H,	CH3),	2.89	(s,	
3H,	CH3),	7.26‐7.48	(m,	14	H,	ArH's).	MS	 (m/e,	%):	518	(M+1,	

4.4%),	 437	 (1.6%),	 390	 (1.8%),	 358	 (1.2%),	 301	 (4%),	 284	
(19.5%),	269	(13%),	242	 (9.5%),	215	(4.9%),	194	(7.25),	154	
(5.8%),	 135	 (17%),	 103	 (10.7%),	 91	 (100%),	 76	 (48%),	 65	
(34%).	Anal.	Calcd.	for	C29H23N7OS	(517.6):	C,	67.29;	H,	4.48;	N,	
18.94;	S,	6.19.	Found:	C,	67.02;	H,	4.62;	N,	18.72;	S,	5.95%.	

3‐{1‐[(5‐Benzoyl‐3‐phenyl‐3H‐[1,3,4]thiadiazol‐2‐ylidene)‐
hydrazono]‐ethyl}‐5‐phenyl‐1‐p‐tolyl‐1H‐pyrazole‐4‐carbonitrile	
(10c):	 Orange	 solid.	 Yield:	 73%.	 M.p.:	 326‐328	 oC.	 IR	 (KBr):	
3040	 (CH,	 aromatic),	 2924	 (CH,	 aliphatic),	 2223	 (CN),	 1663	
(CO),	 1612	 (C=N),	 1370	 (CH3)	 cm‐1.	 	 1H	 NMR	 (200	 MHz,	
(CH3)2SO,	,	ppm):	2.33	(s,	3H,	CH3),	2.56	(s,	3H,	CH3),	7.03‐7.78	
(m,	19	H,	ArH's).	Anal.	Calcd.	for	C34H25N7OS	(579.67):	C,	70.45;	
H,	4.35;	N,	16.91;	S,	5.53.	Found:	C,	70.12;	H,	4.42;	N,	17.22;	S,	
5.52%.	

5‐{[1‐(4‐Cyano‐5‐phenyl‐1‐p‐tolyl‐1H‐pyrazol‐3‐yl)‐ethyl‐
idene]‐hydrazono}‐4‐phenyl‐2‐phenylcarbamoyl‐4,5‐dihydro‐
[1,3,4]thiadiazole	 (10d):	 Yellow	 solid.	 Yield:	 78%.	 M.p.:	 240‐
242	 oC..	 IR	 (KBr,	 cm‐1):	 3428	 (NH),	 3060	 (CH),	 2922	 (CH,	
aliphatic),	2227	(CN),	1675	(CO),	1609	(C=N),	1371	(CH3)	cm‐1.		
1H	NMR	(200	MHz,	(CH3)2SO,	,	ppm):		2.33	(s,	3H,	CH3),	2.73	(s,	
3H,	CH3),	7.26‐7.48	(m,	19	H,	ArH's),	11.72	(s,	br.,	1H,	NH).	MS	
(m/e,	%):	595	(M+,	2.7%),	571	(0.8%),	225	(5.7%),	194	(6.8%),	
150	 (5.1%),	 119	 (14.3%),	 103	 (33.14),	 91	 (89%),	 77	 (100%),	
65	 (49.8%).	 Anal.	 Calcd.	 for	 C34H26N8OS	 (594.69),	 C,	 68.67;	H,	
4.41;	 N,	 18.84;	 S,	 5.39.	 Found:	 C,	 67.02;	 H,	 4.62;	 N,	 18.72;	 S,	
5.95%.	

3‐(1‐{[5‐(4‐Cyano‐5‐phenyl‐1‐p‐tolyl‐2,3‐dihydro‐1H‐pyraz‐
ole‐3‐carbonyl)‐3‐phenyl‐3H‐[1,3,4]thiadiazol‐2‐ylidene]‐hydra‐
zono}‐ethyl)‐5‐phenyl‐1‐p‐tolyl‐1H‐pyrazole‐4‐carbonitrile	
compound	with	ethane	(10e):	Brown:	Yield:	78%.	M.p.:	328‐330	
oC.	 IR	 (KBr,	 cm‐1):	 3045	 (CH,	 aromatic),	 2922	 (CH,	 aliphatic),	
2227	(CN),	1675	(CO),	1609	(C=N),	1371	(CH3)	cm‐1.	 	 1H	NMR	
(200	 MHz,	 (CH3)2SO,	 ,	 ppm):	 2.37	 (s,	 3H,	 CH3),	 2.57	 (s,	 3H,	
CH3),	2.73	(s,	3H,	CH3),	7.26‐7.48	(m,	23	H,	ArH's).	MS	(m/e,	%):	
762	(M+1,	0.5%),	584	(11%),	557	(3%),	284	(70%),	269	(38%),	
256	 (34%),	 242	 (29.6%),	 229	 (12.7%),	 217	 (22%),	 194	
(26.7%),	 	154	(24.5%),	140	(22%),	127	(25.7%),	114	(19.3%),	
103	 (33.14),	 91	 (100%),	77	 (60%),	65	 (52%).	Anal.	 Calcd.	 for	
C45H32N10OS	 (760.87):	 C,	 71.03;	 H,	 4.24;	 N,	 18.41;	 S,	 4.21.	
Found:	C,	67.02;	H,	4.62;	N,	18.72;	S,	5.95%.	
	
2.4.	Synthesis	of	1,3,4‐thiadiazoline	derivatives	(12‐15)	
	

A	mixture	of	the	alkyl	carbodithioate	 	11a‐d	(5	mmol),	the	
appropriate	 hydrazonoyl	 bromide	 4e	 (2.47	 g,	 5	 mmol),	 and	
triethylamine	 (0.75	 mL,	 0.005	 mol)	 in	 ethanol	 (20	 mL)	 was	
stirred	 for	 2	 h	 at	 room	 temperature.	 The	 resulting	 solid	 was	
collected	 and	 recrystallized	 to	 give	 2,3‐dihydro‐1,3,4‐
thiadiazoles	12‐15,	respectively	(Scheme	2).	

3‐{5‐[(1,3‐Diphenyl‐1H‐pyrazol‐4‐ylmethylene)‐hydrazono]‐
4‐phenyl‐4,5‐dihydro‐[1,3,4]thiadiazole‐2‐carbonyl}‐5‐phenyl‐1‐
p‐tolyl‐1H‐pyrazole‐4‐carbonitrile	 (12):	 Red	 solid.	 Yield:	 84%.	
M.p.:	 269‐271	 oC.	 IR	 (KBr,	 cm‐1):	 3056	 (CH,	 aromatic),	 2921	
(CH,	aliphatic),	2230	(CN),	1656	(CO),	1598	(C=C),	1300	(CH3)	
cm‐1.	 	 1H	NMR	(200	MHz,	 (CH3)2SO,	,	ppm):	2.36	(s,	3H,	CH3),	
7.34‐8.04	(m,	26	H,	ArH's).	MS	(m/e,	%):	709	(M+2,	25%),	708	
(M+1,	 40%),	 706	 (M‐1,	 44%),	 479	 (22%),	 448	 (25.9%),	 399	
(22%),	 376	 (29.6%),	 312	 (25.9%),	 287	 (25%),	 286	 (100%),		
232	 (48%),	 231	 (44%),	 215	 (25.9%),	 193	 (25.9%),	 165	
(25.9%),	 164	 (29.6%),	 155	 (40.7%),	 135	 (48%),	 134	 (29%),	
129	 (27%),	 105	 (44%(,	 91	 (48%),	 90	 (66%),	 89	 (40%),	 77	
(100%),	64	(44%).	Anal.	Calcd.	for	C42H29N9OS,	707.8,	C,	71.27;	
H,	4.13;	N,	17.81;	S,	4.53.	Found:	C,	71.62;	H,	4.00;	N,	17.62;	S,	
4.31%.	

3‐(5‐{[1‐(5‐Bromo‐benzofuran‐2‐yl)‐ethylidene]‐hydrazono}‐
4‐phenyl‐4,5‐dihydro‐[1,3,4]thiadiazole‐2‐carbonyl)‐5‐phenyl‐1‐
p‐tolyl‐1H‐pyrazole‐4‐carbonitrile	 (13):	 Brown	 solid.	 Yield:	
81%.		M.p.:		162‐164		oC.		IR	(KBr,	cm‐1):		3052		(CH,	aromatic),		



320	 Abdelhamid	et	al.	/	European	Journal	of	Chemistry	2	(3)	(2011)	317‐323	
	

	  

 
	
	

Scheme	2
	
	

2921	 (CH,	 aliphatic),	 2232	 (CN),	 1665	 (CO),	 1340	 (CH3)	 cm‐1.		
1H	NMR	(200	MHz,	(CH3)2SO,	,	ppm):	2.32	(s,	3H,	CH3),	2.44	(s,	
3H,	CH3),	6.83‐8.18	(m,	18	H,	ArH's).	MS	 (m/e,	%):	699	(M+1,	
29.8%),	697	(M‐1,	30.6%),	412	(16%),	410	(15%),	286	(100%),	
249	 (19.2%),	 274	 (18%),	 222	 (12%),	 220	 (	 11.6%),	 196	
(38.5%),	194	(37.4%),	91	(57.7%),	90	(23.1%),	77	(15.4%),	65	
(46.2%).	 Anal.	 Calcd.	 for	 C36H24BrN7O2S	 (698.59)	 C,	 61.89;	 H,	
3.46;	Br,	11.44;	N,	14.03;	S,	4.59.	Found:	C,	61.73;	H,	3.67;	Br,	
11.23;	N,	14.25;	S,	4.70%.	

3‐(5‐{[1‐(2‐Oxo‐2H‐chromen‐3‐yl)‐ethylidene]‐hydrazono}‐4‐
phenyl‐4,5‐dihydro‐[1,3,4]thiadiazole‐2‐carbonyl)‐5‐phenyl‐1‐p‐
tolyl‐1H‐pyrazole‐4‐carbonitrile	 (14):	Brown	 solid.	 Yield:	 78%.	
M.p.:	 162‐164	 oC.	 IR	 (KBr,	 cm‐1):	 3057	 (CH,	 aromatic),	 2926	
(CH,	 aliphatic),	 2230	 (CN),	 1715,	 1665	 (CO),	1342	 (CH3)	 cm‐1.		
1H	NMR	(200	MHz,	(CH3)2SO,	,	ppm):	2.37	(s,	3H,	CH3),	2.45	(s,	
3H,	CH3),	6.83‐8.18	(m,	19	H,	ArH's).	MS	 (m/e,	%):	648	(M+1,	
30.8%),	 647	 (M+,	 34.6%),	 286	 (100%),	 225	 (19.2%),	 196	
(38.5%),	 145	 (26.9%),	 119	 (38.5%),	 91	 (57.7%),	 90	 (23.1%),	
77	(15.4%),	65	(46.2%).	Anal.	Calcd.	for	C37H25N7O3S	(647.7)	C,	
68.61;	 H,	 3.89;	 N,	 15.14;	 S,	 4.95.	 Found:	 C,	 68.45;	 H,	 4.10;	 N,	
15.00;	S,	4.72%.	

3‐(5‐{[1‐(3‐Oxo‐3H‐benzo[f]chromen‐2‐yl)‐ethylidene]‐
hydrazono}‐4‐phenyl‐4,5‐dihydro‐[1,3,4]thiadiazole‐2‐carbonyl)‐
5‐phenyl‐1‐p‐tolyl‐1H‐pyrazole‐4‐carbonitrile	 (15):	 Orange	
solid.	 Yield:	 78%.	M.p.:	 258‐260	 oC.	 IR	 (KBr,	 cm‐1):	 3051	 (CH,	
aromatic),	 2920	 (CH,	 aliphatic),	 2232	 (CN),	 1666	 (CO),	 1723,	
1667	 (CO),	 1340	 (CH3)	 cm‐1.	 	 1H	NMR	 (200	MHz,	 (CH3)2SO,	,	
ppm):	2.76	 (s,	3H,	CH3),	2.91	 (s,	3H,	CH3),	 6.83‐8.18	 (m,	21	H,	
ArH's).	MS	(m/e,	%):	698	(M+1,	30.8%),	679	(M+,	34.6%),	286	
(100%),	225	(19.2%),	194	(38.5%),	155	(26.9%),	139	(38.5%),	
91	 (57.7%),	 90	 (23.1%),	 77	 (15.4%),	 65	 (46.2%).	Anal.	 Calcd.	
for	 C41H27N7O3S	 (697.76)	 C,	 70.57;	 H,	 3.90;	 N,	 14.05;	 S,	 4.60.	
Found:	C,	70.75;	H,	3.73;	N,	13.82;	S,	4.75%.	

	

2.5.	Synthesis	of	ethyl	3‐(4‐Cyano‐1,5‐diphenyl‐1H‐pyrazole‐
3‐carbonyl)‐6‐methyl‐1‐phenyl‐4‐substituted	3a,4‐dihydro‐
1H‐indazole‐5‐carboxylate	(19a‐e),	[1,2,4]triazolo[3,4‐b]	
quinazolin‐5‐one	(21),	1H‐benzo[4,5]imidazo[2,1‐c][1,2,4]	
triazol‐3‐yl)‐methanone	(22)	and	1,2,3a,10‐tetraaza‐cyclo‐
penta[b]fluoren‐4‐one	(23)	
			

Method	A:	A	mixture	of	the	hydrazonoyl	bromide	4e	(2.47	g,	
5	 mmol)	 and	 the	 appropriate	 of	 pyrimidine‐2‐thione	
derivatives	 [26]	 16a‐e,	 2‐thioxo‐2,3‐dihydro‐1H‐quinazolin‐4‐
one,	 2‐thioxo‐2,3,5,6,7,8‐hexahydro‐1H‐benzo[4,5]thieno[2,3‐
d]‐pyrimidin‐4‐one,	or	2‐mercaptobenzimidazole	 	(5	mmol)	 in	
chloroform	(20	mL)	containing	triethylamine	(0.5	g	(0.75	mL),	
5	 mmol)	 was	 refluxed	 for	 20	 h.	 Chloroform	 was	 evaporated	
under	 reduced	 pressure	 and	 the	 remaining	 solid	 was	
crystallized	from	ethanol	to	give	ethanol	to	give	19a‐d,	and	21‐
23,	respectively	(Scheme	3	and	4).	

Method	 B:	 A	 mixture	 of	 the	 appropriate	 hydrazonoyl	
bromide	 4e	 (2.47	 g,	 5	 mmol),	 the	 appropriate	 of	 20a‐e	 (5	
mmol),	 and	 sodium	 ethoxide	 (0.34	 g,	 5	mmol)	 in	 ethanol	 (20	
mL)	was	 refluxed	 for	 3	 hrs.	 The	 reaction	mixture	was	 cooled	
and	 the	 resulting	 solid	 was	 collected	 and	 crystallized	 from	
dioxane	gave	products	identical	in	all	aspects	(m.p.,	mixed	m.p.,	
and	spectra)	with	corresponding	products	obtained	by	Method	
A	(Scheme	3	and	4).	

Ethyl	 3‐(4‐cyano‐1,5‐diphenyl‐1H‐pyrazole‐3‐carbonyl)‐7‐
methyl‐1,5‐diphenyl‐1,5‐dihydro‐[1,2,4]triazolo[4,3‐a]pyrimi‐
dine‐6‐carboxylate	 (19a):	 Pale	 brown.	 Yield:	 84%.	 M.p.:	 178‐
180	 oC.	 IR	 (KBr,	 cm‐1):	 3050	 (CH,	 aromatic),	 2924	 (CH,	
aliphatic),	2235	(CN),	1666	(CO),	1609	(C=C),	1372	(CH3)	cm‐1.		
1H	 NMR	 (200	 MHz,	 (CH3)2SO,	 ,	 ppm):	 1.13	 (t,	 3H,	 J	 =	 7	 Hz,	
CH2CH3),	2.29	(s,	3H,	CH3),	2.49	(s,	3H,	CH3),	4.03	(q,	2H,	 J	=	7	
Hz,	CH2CH3),	6.53	(s,	1H),	7.23‐8.18	(m,	19	H,	ArH's).	

	
	



Abdelhamid	et	al.	/	European	Journal	of	Chemistry	2	(3)	(2011)	317‐323	 321	
 

 
 

 

N

R Br

NH

Ph
N
H

NHO

O

S

R'

+ N

R

N

Ph

N

NHO

O

S

R'

R

N
HN

Ph

N
H

NHO

O R'

N N

S

Ph

R

N

NO

O R'

N
N

R

PhN

NHO

O

S

R'

CH3

16 4e
5e

17
18

19

20
16-20a, R' = C6H5

b, R' = 4-CH3C6H4
c, R' = 2,3-OCH2OC6H3
d, R' = 4-(CH3)2CHC6H4

4e

R = 5-phenyl-1-p-tolyl-1H-pyrazolyl-4-carbonitrile 	
	

Scheme	3
	
	
MS	 (m/e,	 %):	 647	 (M+2,	 25%),	 646	 (M+1,	 50%),	 645	 (M+,	
75%),	 628	 (65%),	 569	 (25%),	 568	 (75%),	 567	 (60%),	 426	
(40%),	 334	 (40%),	 333	 (50%),	 332	 (35%),	 286	 (45%),	 	 285	
(40%),	 225	 (45%),	 223	 (35%),	 222	 (60%),	 169	 (55%),	 117	
(30%),	 116	 (65%),	 114	 (45%),	 101	 (100%),	 94	 (25%),	 93	
(25%),	92	(30%),	91	(30%),	80	(50%),	79	(40%),	77	(100%),	
65	 (90%).	 Anal.	 Calcd.	 for	 C39H31N7O3	 (645.71):	 C,	 72.54;	 H,	
4.84;	N,	15.18.	Found:	C,	72.41;	H,	4.68;	N,	15.31%.	

Ethyl	 3‐(4‐cyano‐1,5‐diphenyl‐1H‐pyrazole‐3‐carbonyl)‐7‐
methyl‐1‐phenyl‐5‐p‐tolyl‐1,5‐dihydro‐[1,2,4]triazolo[4,3‐a]	
pyrimidine‐6‐carboxylate	(19b):	Brown	solid.	Yield:	85%.	M.p.:	
144‐146	 oC.	 IR	 (KBr,	 cm‐1):	 3035	 (CH,	 aromatic),	 2924	 (CH,	
aliphatic),	2233	(CN),	1670	(CO),	1600	(C=C),	1446	(CH2),	1373	
(CH3)	cm‐1.		1H	NMR	(200	MHz,	(CH3)2SO,	,	ppm):	1.18	(t,	3H,	J	
=	7	Hz,	CH2CH3),	2.2.0	(s,	3H,	CH3),	2.28	(s,	3H,	CH3),	2.49	(s,	3H,	
CH3),	4.04	(q,	2H,	J	=	7	Hz,	CH2CH3),	6.37	(s,	1H),	7.23‐8.21	(m,	
18	 H,	 ArH's).	 MS	 (m/e,	%):	 660	 (M+1,	 0.68%),	 644	 (1.18%),	
512	(8.69%),	484	(3.12%),	406	(4%),	297	(6.5%),	286	(33.6%),	
270	 (11.7%),	 258	 (29.8%),	 242	 (20.8%),	 215	 (11%),	 194	
(16.7%),	 	 170	 (11.2%),	 155	 (15.9%),	 140	 (21.8%),	 114	
(28.8%),	 102	 (43.5%),	 77	 (100%),	 76	 (73%).	 Anal.	 Calcd.	 for	
C40H33N7O3	 (659.74):	 C,	 72.82;	 H,	 5.04;	 N,	 14.86.	 Found:	 C,	
73.01;	H,	4.88;	N,	14.68%.	

Ethyl	 5‐benzo[1,3]dioxol‐4‐yl‐3‐(4‐cyano‐1,5‐diphenyl‐1H‐
pyrazole‐3‐carbonyl)‐7‐methyl‐1‐phenyl‐1,5‐dihydro‐[1,2,4]	
triazolo[4,3‐a]pyrimidine‐6‐carboxylate	 (19c):	 Brown	 solid.	
Yield:	 86%.	 M.p.:	 169‐171	 oC.	 IR	 (KBr,	 cm‐1):	 3035	 (CH,	
aromatic),	 2921	 (CH,	 aliphatic),	 2235	 (CN),	 1671	 (CO),	 1607	
(C=C),	 1444	 (CH2),	 1373	 (CH3)	 cm‐1.	 	 1H	 NMR	 (200	 MHz,	
(CH3)2SO,	,	 ppm):	 1.15	 (t,	 3H,	 J	 =	 7	Hz,	 CH2CH3),	 2.30	 (s,	 3H,	
CH3),	2.49	(s,	3H,	CH3),	4.04	(q,	2H,	 J	=	7	Hz,	CH2CH3),	5.95	(s,	
2H,	OCH2O),	6.15	(s,	1H),	7.23‐8.21	(m,	17	H,	ArH's).	MS	(m/e,	
%):	689	(M+,	1.01%),	572	(1.29%),	556	(2.18%),	512	(1.52%),	
445	 (1.56%),	 377	 (1.17%),	 357	 (1.54%),	 286	 (5.28%),	 244	

(2.65%),	149	(14.8%),	104	(20.55%),	91	(65.2%),	77	(100%),	
69	 (31%).	 Anal.	 Calcd.	 for	 C40H31N7O5	 (689.72):	 C,	 69.66;	 H,	
4.53;	N,	14.22.	Found:	C,	69.85;	H,	4.34;	N,	14.10%.	

Ethyl	 3‐(4‐cyano‐1,5‐diphenyl‐1H‐pyrazole‐3‐carbonyl)‐5‐
(1,3‐diphenyl‐1H‐pyrazol‐4‐yl)‐7‐methyl‐1‐phenyl‐1,5‐dihydro‐
[1,2,4]triazolo[4,3‐a]pyrimidine‐6‐carboxylate	 (19d):	 Pale	
brownsolid.	Yield:	85%.	M.p.:	202‐204	oC	(AcOH).	IR	(KBr,	cm‐

1):	3033	(CH,	aromatic),	2963	(CH,	aliphatic),	2234	(CN),	1662	
(CO),	1605	(C=C),	1431	(CH2),	1369,	1321	(CH3)	cm‐1.		1H	NMR	
(200	MHz,	(CH3)2SO,	,	ppm):	1.09	(d,	6H,	J	=	8	Hz,	(CH(CH3)2,	
1.18	(t,	3H,	J	=	7	Hz,	CH2CH3),	2.30	(s,	3H,	CH3),	2.40	(s,	3H,	CH3),	
2.85	 (sept,	 1H,	 J	 =	 8	 Hz,	 CH(CH3)2),	 4.10	 (q,	 2H,	 J	 =	 7	 Hz,	
CH2CH3),	6.15	(s,	1H),	7.23‐8.21	(m,	18	H,	ArH's).	MS	(m/e,	%):	
689	 (M+2,	 12.2%),	 688	 (M+1,	 53.8%),	 687	 (M+,	 71%),	 668	
(17.3%),	614	(84.6%),	569	(33.3%),	541	(18.6%),	375	(100%),	
287	 (43.6%),	 286	 (87.8%),	 243	 (27.6%),	 194	 (16%),	 155	
(41.7%),	154	(24.4%),	141	(14.7%),	118	(19.9%),	105	(21.8%),	
104	(19.2%),	103	(17.9%),	101	(16%),	91	(48.1%),	90	(19%),	
78	(12.2%),	77	(53.2%),	66	(8.3%).	Anal.	Calcd.	for	C42H37N7O3	
(687.79):	C,	73.34;	H,	5.42;	N,	14.26.	Found:	C,	73.58;	H,	5.71;	N,	
14.10%.	

Ethyl	 3‐(4‐cyano‐5‐phenyl‐1‐p‐tolyl‐1H‐pyrazole‐3‐
carbonyl)‐5‐(1,3‐diphenyl‐1H‐pyrazol‐4‐yl)‐7‐methyl‐1‐phenyl‐
1,5‐dihydro‐[1,2,4]triazolo[4,3‐a]pyrimidine‐6‐carboxylate	
(19e):	Pale	brown	solid.	Yield:	80%.	M.p.:	142‐144	oC.	IR	(KBr):	
3033	 (CH,	 aromatic),	 2963	 (CH,	 aliphatic),	 2234	 (CN),	 1662	
(CO),	1605	(C=C),	1431	(CH2),	1369,	1321	(CH3)	cm‐1.	 1H	NMR	
(200	MHz,	(CH3)2SO,	,	ppm):	1.18	(t,	3H,	J	=	7	Hz,	CH2CH3),	2.30	
(s,	 3H,	 CH3),	 2.40	 (s,	 3H,	 CH3),	 4.10	 (q,	 2H,	 J	 =	 7	Hz,	 CH2CH3),	
6.15	 (s,	 1H),	 7.23‐8.21	 (m,	 25	 H,	 ArH's).	 Anal.	 Calcd.	 for	
C48H37N9O3	 (787.87):	 C,	 73.17;	 H,	 4.73;	 N,	 16.00.	 Found:	 C,	
73.32;	H,	4.52;	N,	16.21%.	

	
	



322	 Abdelhamid	et	al.	/	European	Journal	of	Chemistry	2	(3)	(2011)	317‐323	
	

	

N

R Br

NH

Ph

4e

N

N

O

N
N

Ph

O
R

S
N

N
O

N

N

Ph

O
R

N

N
N

N

Ph

O
R

21

22

23

a

b

c

R =5-phenyl-1-p-tolyl-1H-pyrazolyl-4-carbonitrile
R = 4-cyano-5-phenyl-1-p-tolyl-1H-pyrazol-3-yl
a = 2-thioxo-2,3-dihydro-1H-quinazolin-4-one
b = 2-thioxo-2,3,5,6,7,8-hexahydro-1H-benzo[4,5]thieno[2,3-d]pyrimidin-4-one
c = 2-mercaptobenzimidazole 	

Scheme	4	

	 
	

3‐(5‐Oxo‐1‐p‐tolyl‐1,5‐dihydro‐[1,2,4]triazolo[3,4‐b]	
quinazoline‐3‐carbonyl)‐1,5‐diphenyl‐4,5‐dihydro‐1H‐pyrazole‐
4‐carbonitrile	(21):	Pale	brown	solid.	Yield:	80%.	M.p.:	180‐182	
oC.	 IR	 (KBr):	 3033	 (CH,	 aromatic),	 2963	 (CH,	 aliphatic),	 2233	
(CN),	1675	(CO),	1605	(C=C),	1431	(CH2),	1369,	1321	(CH3)	cm‐

1.		1H	NMR	(200	MHz,	(CH3)2SO,	,	ppm):	2.36	(s,	3H,	CH3),	7.23‐
8.21	 (m,	18	H,	ArH's).	Anal.	 Calcd.	 for	C33H21N7O2	 (547.57):	 C,	
72.38;	H,	3.87;	N,	17.91.	Found:	C,	72.42;	H,	4.05;	N,	18.10%.	

3‐(4‐Oxo‐1‐p‐tolyl‐1,4,5,6,7,8‐hexahydro‐9‐thia‐1,2,3a,10‐
tetraaza‐cyclopenta[b]fluorene‐3‐carbonyl)‐1,5‐diphenyl‐4,5‐
dihydro‐1H‐pyrazole‐4‐carbonitrile	 (22):	 Yellow	 solid.	 Yield:	
68%.	 M.p.:	 136‐138	 oC.	 IR	 (KBr,	 cm‐1):	 3045	 (CH,	 aromatic),	
2968	(CH,	aliphatic),	2233	(CN),	1666	(CO),	1600	(C=C),	1435	
(CH2),	1370,	(CH3)	cm‐1.		1H	NMR	(200	MHz,	(CH3)2SO,	,	ppm):	
1.61‐1.85	(m,	4H),	2.80‐2.95	(m,	4H),	2.41	(s,	3H,	CH3),	7.23	(t,	
1H,		J	=	8	Hz,	ArH's),	7.41	(s,	1H,	ArH),	7.42‐7.52	(m,	2H,	ArH,s),	
7.89	(d,	1H,	J	=	8	Hz,	ArH),	8.12	(d,	1H,	J	=	8	Hz,	ArH),	8.19	(m,	
7H,	ArH's),	8.38	(s,	1H,	ArH).	MS	(m/e,	%):	6.7	(M+,	4.79%),	510	
(4.11%),	 489	 (7.53%),	 462	 (12.30%),	 429	 (5.73%),	 312	
(5.70%),	286	(100%),	243	(7.12%),	91	(78.12%),	77	(74.25%),	
65	(56.57%).	Calcd.	for	C35H25N7O2S	(607.68):	C,	69.18;	H,	4.15;	
N,	16.13;	S,	5.28.	Found:	C,	69.12;	H,	4.23;	N,	16.11;	S,	5.42%.	

5‐Phenyl‐3‐(1‐phenyl‐1H‐benzo[4,5]imidazo[2,1‐c][1,2,4]	
triazole‐3‐carbonyl)‐1‐p‐tolyl‐1H‐pyrazole‐4‐carbonitrile	 (23):	
Pale	brown.	Yield:	72%.	M.p.:	168‐188	oC.	IR	(KBr,	cm‐1):	3033	
(CH,	 aromatic),	 2963	 (CH,	 aliphatic),	 2233	 (CN),	 1716	 (CO),	
1616	(C=C),	1338,	(CH3)	cm‐1.	 	1H	NMR	(200	MHz,	(CH3)2SO,	,	
ppm):	 2.31	 (s,	 3H,	 CH3),	 7.26‐8.21	 (m,	 18	H,	ArH's).	MS	 (m/e,	
%):	519	(M+,	0.27%),	312	(5.37%),	286	(6.19%),	251	(6.92%),	
225	 (21.48%),	 187	 (5.11%),	 167	 (6.28%),	 149	 (6.50%),	 135	
(10.31%),	 108	 (9.15%),	 102	 (26.51%),	 91	 (45.02%),	 76	
(100%),	 65	 (33.82%).	 Anal.	 Calcd.	 for	 C32H21N7O	 (519.56):	 C,	
73.98;	H,	4.07;	N,	18.87.	Found:	C,	73.72;	H,	3.88;	N,	18.64%.	
	
3.	Results	and	discussion	
	

Methyl	 2‐[1‐(4‐cyano‐1,5‐diphenyl‐1H‐pyrazol‐3‐yl)ethyl‐
idene]hydrazine‐carbodithioate	(3a)	and	benzyl	2‐[1‐(4‐cyano‐
1,5‐diphenyl‐1H‐pyrazol‐3‐yl)ethylidene]hydrazine	 carbodi	
thioate	 (3b)	 reacted	 with	 ethyl	 2‐chloro(phenylhydrazono)	
acetate	 (4a)	 to	 afford	 ethyl	 5‐{[1‐(4‐methyl‐1,5‐diphenyl‐1H‐

pyrazol‐3‐yl)‐ethylidene]‐hydrazono}‐4‐phenyl‐4,5‐dihydro‐
[1,3,4]thiadiazole‐2‐carboxylate	(8a)	(Scheme	1).	Structure	8a	
was	 confirmed	 by	 elemental	 analysis,	 spectra	 and	 alternative	
synthetic	route.		

Thus,	 treatment	 of	 ethyl	 2‐hydrazino‐3‐phenyl‐2,3‐
dihydro‐1,3,4‐thiadiazole‐5‐carboxylate	(9a)	with	3‐acetyl‐1,5‐
diphenyl‐1H‐pyrazole‐4‐carbonitrile	 (1a)	 gave	 a	 product	
identical	 in	all	aspects	(m.p.,	mixed	m.p.	and	spectra)	with	8a.	
The	formation	of	8a	 is	assumed	to	proceed	via	1,3‐addition	of	
thiol	 tautomer	of	carbodithioate	3a	 (or	3b)	 to	nitrilium	 imide	
5a	 (generated	 in	 situ	 by	 treatment	 of	4a	with	 triethylamine)	
can	give	6a,	 nucleophilic	 cyclization	 to	yield	7a.	Alternatively,	
1,3‐cycloaddition	 of	 nitrilium	 imide	 5a	 to	 the	 C=S	 of	
carbodithioate	3a	(or	3b)	can	give	7a	directly,	and	then	afford	
8a	 by	 loss	 of	 alkyl	 mercaptan	 (Scheme	 1).	 Analogously,	
treatment	of	the	appropriate	4b‐e	with	the	appropriate	3a‐d	in	
ethanolic	triethylamine	gave	thiadiazoline	derivatives	8b‐e	and	
10b‐e,	respectively.	

Similarly,	 	 treatment	 of	 2‐(4‐cyano‐1,5‐diphenyl‐1H‐
pyrazol‐3‐yl)‐2‐oxo‐N‐phenylethanehydrazonoyl	 bromide	 (4e)	
with	the	appropriate	11a‐e	gave	{5‐[(2,5‐diphenyl‐2H‐pyrazol‐
3‐ylmethylene)‐hydrazono]‐4‐p‐tolyl‐4,5‐dihydro‐[1,3,4]‐thia‐
diazol‐2‐yl}‐(4‐methyl‐1,5‐diphenyl‐1H‐pyrazol‐3‐yl)‐methan‐
one	 (12),	 {5‐[(1‐benzofuran‐3‐yl‐ethylidene)‐hydrazono]‐4‐p‐
tolyl‐4,5‐dihydro‐[1,3,4]thiadiazol‐2‐yl}‐(4‐methyl‐1,5‐di‐
phenyl‐1H‐pyrazol‐3‐yl)‐methanone	 (13),	 3‐(1‐{[5‐(4‐methyl‐
1,5‐diphenyl‐1H‐pyrazole‐3‐carbonyl)‐3‐p‐tolyl‐3H‐[1,3,4]	
thiadiazol‐2‐ylidene]‐hydrazono}‐ethyl)‐chromen‐2‐one	 (14)	
and	 2‐(1‐{[5‐(4‐methyl‐1,5‐diphenyl‐1H‐pyrazole‐3‐carbonyl)‐
3‐p‐tolyl‐3H‐[1,3,4]thiadiazol‐2‐ylidene]‐hydrazono}‐ethyl)‐
benzo[f]chromen‐3‐one	(15),	respectively	(Scheme	2).	

Also,	treatment	of	4e	with	each	of	the	pyrimidine‐2‐thione	
16	 and	 21	 in	 boiling	 chloroform	 gave	 triazolino[4,3‐
a]pyrimidines	in	a	good	yields	20a‐e,	respectively	(Scheme	3).	
Structure	of	20	was	elucidated	by	elemental	analysis,	 spectral	
data	and	alternative	synthetic	route.	Thus,	1H	NMR	spectrum	of	
20a	showed	signals	at		=	1.23	(t,	3H,	CH2CH3),	2.24	(s,	CH3,	4‐
CH3C6H4),	 2.56	 (s,	 3H,	 CH3),	 4.09	 (q,	 2H,	 CH2CH3),	 5.05	 (s,	 1H,	
pyrimidine	 H‐4),	 7.44‐8.24	 (m,	 19H,	 ArH's).	 Its	 IR	 spectrum	
revealed	bands	at	1702	(CO	ester),	1650	(CO	conjugated)	and	
1615	(C=N).	



Abdelhamid	et	al.	/	European	Journal	of	Chemistry	2	(3)	(2011)	317‐323	 323	
 

 
 

Furthermore,	 compound	 20a	 was	 obtained	 from	 the	
reaction	 of	 ethyl	 6‐methy‐2‐methylthio‐4‐phenyl‐3,4‐dihydro‐
pyrimidine‐5‐carboxylate	 21	 with	 11	 in	 boiling	 sodium	
ethoxide	solution.	The	mechanism	outlined	in	Scheme	3	seems	
to	be	the	most	plausible	pathway	for	the	formation	of	20	from	
the	 reaction	 of	 11	 with	 16	 or	 21.	 1,3‐Addition	 of	 the	 thiol	
tautomer	 16	 to	 the	 nitrilium	 imide	 17	 to	 give	 the	
thiohydrazonate	 ester	 18	 which	 undergoes	 nucleophilic	
cyclization	 to	 yield	 spiro	 compounds	19.	 The	 latter	 ring	 open	
and	 cyclized	 to	yield	20	 by	 loss	 hydrogen	 sulfide;	 and	2)‐1,3‐
cycloaddition	of	nitrilium	imide	17	to	C=S	double	bond	of	16	to	
give	 directly	 19	 (Scheme	 3).	 All	 attempts	 to	 isolate	 any	
intermediates	were	unsuccessful.	

Analogously,	 reactions	 of	 2‐thioxo‐2,3‐dihydro‐1H‐
quinazolin‐4‐one	 [21],	 2‐thioxo‐2,3,5,6,7,8‐hexahydro‐1H‐
benzo[4,5]thieno[2,3‐d]pyrimidin‐4‐one	 [22],	 or	 2‐mercapto‐
benzimidazole	with	hydrazonoyl	bromide	4e	were	carried	out	
in	 refluxing	 chloroform	 in	 presence	 of	 TEA	 gave	
[1,2,4]triazolo[3,4‐b]quinazolin‐5‐one	 21,	 1H‐benzo[4,5]	
imidazo[2,1‐c][1,2,4]triazol‐3‐yl)‐methanone	22	and	1,2,3a,10‐
tetraaza‐cyclopenta[b]fluoren‐4‐one	 23,	 respectively	 (Scheme	
4).	
	
4.	Conclusion	
	

The	 studies	 described	 above	 clearly	 demonstrate	 that	 the	
new	2,3‐dihydro‐1,3,4‐thiadiazole,	 triazolino[4,3‐a]pyrimidine,	
triazolo[3,4‐b]quinazolin‐5‐one,	 1H‐benzo[4,5]imidazo[2,1‐c]	
[1,2,4]triazol‐3‐yl)‐methanone,	 and	 1,2,3a,10‐tetraaza‐cyclo‐
penta[b]fluoren‐4‐one	 23	 derivatives	 containing	 pyrazole	
moiety	 can	 be	 synthesized	 in	 a	 good	 yield	 via	 hydrazonoyl	
halides.	
	
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